Drug resistance mechanisms in cancers:Execution of prosurvival strategies

One of the quintessential challenges in cancer treatment is drug resistance.Several mechanisms of drug resistance have been described to date,and new modes of drug resistance continue to be discovered.The phenomenon of cancer drug resistance is now widespread,with approximately 90% of cancer-related deaths associated with drug resistance.Despite significant advances in the drug discovery process,the emergence of innate and acquired mechanisms of drug resistance has impeded the progress in cancer therapy.Therefore,understanding the mechanisms of drug resistance and the various pathways involved is integral to treatment modalities.In the present review,I discuss the different mechanisms of drug resistance in cancer cells,including DNA damage repair,epithelial to mesenchymal transition,inhibition of cell death,alteration of drug targets,inactivation of drugs,deregulation of cellular energetics,immune evasion,tumor-promoting inflammation,genome instability,and other contributing epigenetic factors.Furthermore,I highlight available treatment options and conclude with future directions.

Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Assessment and Visualization of Ki67 Heterogeneity in Breast Cancers through Digital Image Analysis

The Ki67 index (KI) is a standard clinical marker for tumor proliferation;however, its application is hindered by intratumoral heterogeneity. In this study, we used digital image analysis to comprehensively analyze Ki67 heterogeneity and distribution patterns in breast carcinoma. Using Smart Pathology software, we digitized and analyzed 42 excised breast carcinoma Ki67 slides. Boxplots, histograms, and heat maps were generated to illustrate the KI distribution. We found that 30% of cases (13/42) exhibited discrepancies between global and hotspot KI when using a 14% KI threshold for classification. Patients with higher global or hotspot KI values displayed greater heterogenicity. Ki67 distribution patterns were categorized as randomly distributed (52%, 22/42), peripheral (43%, 18/42), and centered (5%, 2/42). Our sampling simulator indicated analyzing more than 10 high-power fields was typically required to accurately estimate global KI, with sampling size being correlated with heterogeneity. In conclusion, using digital image analysis in whole-slide images allows for comprehensive Ki67 profile assessment, shedding light on heterogeneity and distribution patterns. This spatial information can facilitate KI surveys of breast cancer and other malignancies.

Modeling human gastric cancers in immunocompetent mice

Gastric cancer(GC)is a major cause of cancer-related mortality worldwide.GC is determined by multiple(epi)genetic and environmental factors;can occur at distinct anatomic positions of the stomach;and displays high heterogeneity,with different cellular origins and diverse histological and molecular features.This heterogeneity has hindered efforts to fully understand the pathology of GC and develop efficient therapeutics.In the past decade,great progress has been made in the study of GC,particularly in molecular subtyping,investigation of the immune microenvironment,and defining the evolutionary path and dynamics.Preclinical mouse models,particularly immunocompetent models that mimic the cellular and molecular features of human GC,in combination with organoid culture and clinical studies,have provided powerful tools for elucidating the molecular and cellular mechanisms underlying GC pathology and immune evasion,and the development of novel therapeutic strategies.Herein,we first briefly introduce current progress and challenges in GC study and subsequently summarize immunocompetent GC mouse models,emphasizing the potential application of genetically engineered mouse models in antitumor immunity and immunotherapy studies.

Epidemiological and Anatomo Path Ological Aspects of Stomach Cancers at the Koutiala District Hospital

Aim: This paper aims to evaluate the epidemiological and pathological aspects of stomach cancer at Koutiala District Hospital. Methods: This was a retrospective study carried out in the General Surgery Department of the Koutiala District Hospital Health Centre. The records of patients admitted for stomach cancer in the period from August 1, 2017 to December 31, 2022 were collected. Patients who underwent surgery for stomach cancer were included in the study. Patients who had not undergone surgery were excluded. Results: We collected records from 40 patients operated on for stomach cancer. The median age was 58.4 years ± 5.7. Men were in the majority with 72.5% The sex ratio was 2.6. The incidence rate of stomach cancer in the general population in the circle was 4.9 cases per 100,000 population. Patients had a history of gastric ulcer in 90%, Helicobacter pylori infection in 47.5% and a notion of excessive salt consumption in 47.5%. The median duration of disease progression was 5 years ± 2.3. The seat was antro-pyloric in 77.5%. The cancer was ulcerative budding in 23 patients. Adenocarcinoma was the histological type in all patients. The cancer was classified as stage III in 30 cases and stage IV in 10 cases. Palliative surgical treatment was the most performed (47.5%). Postoperative morbidity was 15% and mortality was 42.5% at one year. Conclusion: Stomach cancer is common in the ward. Most patients consult at the stage of metastasis. Palliative surgery remains the most practical. Postoperative morbidity and mortality is very high.

Nursing of a patient with multiple primary cancers: A case report and review of literature

BACKGROUND Although the occurrence of multiple primary cancers(MPC)is not exceedingly common,it is not rare in clinical practice.In recent years,there has been a notable increase in its incidence.The frequent confusion between MPC and tumor metastasis or recurrence often leads to delays in diagnosis and treatment.This study aimed to enhance understanding of MPC,improve diagnostic accuracy,guide precise clinical treatment,and implement a case management nursing model(CMNM)to facilitate quick patient recovery.CASE SUMMARY A 61-year-old female patient presented with persistent upper abdominal pain lasting over 2 months.Gastroscopy revealed the presence of both gastric and duodenal cancers.Following a thorough evaluation,the patient underwent pancreaticoduodenectomy,cholecystectomy,and total gastrectomy.Post-surgery,an individualized case management nursing approach was applied,leading to a successful recovery.Three months after the surgery,follow-up examinations showed no signs of recurrence.CONCLUSION The CMNM effectively promoted rapid patient recovery,enhanced the quality of orthopedic nursing services,and accelerated postoperative recovery,ultimately leading to increased patient satisfaction with nursing care.

Synthesis and Physico-Chemical Characterizations of Novel Hydrazone Ligands and Their Metal Complexes against Hormone-Dependent and Independent Cancers

This work deals with the synthesis and physicochemical characterizations of a new group of novel retinoidal ligands and their metal complexes. Their in vitro anti-proliferative activities have shown that ligand L1 is effective against human breast cancer BT-20 and MCF-7 cell lines. At the same time, compound L2 exerts its effect on human prostate cancer PC-3 and human breast cancer MDA-MB-231 and MCF-7 cell lines respectively. The retinoid ligands exert their pleiotropic action toward retinoic acid receptors (RARs) than their metal complexes but all compounds exhibit concentration-dependent.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Unique Clinical Features of Curaderm when Treating Skin Cancers

Basal cell carcinoma is the most common form of skin cancer and the most frequently occurring form of all cancers. Conventional treatments to remove or destroy basal cell carcinoma are indiscriminate and also remove or destroy normal skin cells resulting in compromised cosmetic outcomes. Consequences of these treatments include body-image issues, anxiety, post-traumatic stress disorder, depression, and poorer quality of social and family life. A progressive topical cream formulation, Curaderm, containing the natural BEC glycoalkaloids, have shown to have advantages over conventional treatments. However, comprehensive clinical features of the skin cancer lesions during treatment with Curaderm have to date not been reported. This report shows that using unpublished data from a large number of patients with varying sizes, types and locations of basal cell carcinomas when treated with Curaderm in a phase 3 trial, an initial increase in size of the lesions occur, followed by a reverse course, leading to complete removal of the skin cancer. The specificity and mode of action of Curaderm explains the superior cosmetic outcomes when compared with conventional therapies.

A Comprehensive Study of the Association between LEPR Gene rs1137101 Variant and Risk of Digestive System Cancers

Objective The leptin receptor,encoded by the LEPR gene,is involved in tumorigenesis.A potential functional variant of LEPR,rs1137101(Gln223Arg),has been extensively investigated for its contribution to the risk of digestive system(DS)cancers,but results remain conflicting rather than conclusive.Here,we performed a case–control study and subsequent meta-analysis to examine the association between rs1137101 and DS cancer risk.Methods A total of 1,727 patients with cancer(gastric/liver/colorectal:460/480/787)and 800 healthy controls were recruited.Genotyping of rs1137101 was conducted using a polymerase chain reactionrestriction fragment length polymorphism(PCR-RFLP)assay and confirmed using Sanger sequencing.Twenty-four eligible studies were included in the meta-analysis.Results After Bonferroni correction,the case–control study revealed that rs1137101 was significantly associated with the risk of liver cancer in the Hubei Chinese population.The meta-analysis suggested that rs1137101 is significantly associated with the risk of overall DS,gastric,and liver cancer in the Chinese population.Conclusion The LEPR rs1137101 variant may be a genetic biomarker for susceptibility to DS cancers(especially liver and gastric cancer)in the Chinese population.

Interleukin-1β:Friend or foe for gastrointestinal cancers

Gastrointestinal(GI)cancer is a malignancy arising in the digestive system and accounts for approximately a third of increasing global cancer-related mortality,especially in the colorectum,esophagus,stomach,and liver.Interleukin-1β(IL-1β)is a leukocytic pyrogen recognized as a tumor progression-related cytokine.IL-1βsecretion and maturation in inflammatory responses could be regulated by nuclear factor-kappaB-dependent expression of NLR family pyrin domain containing 3,inflammasome formation,and activation of IL-1 converting enzyme.Several studies have documented the pro-tumorigenic effects of IL-1β in tumor microenvironments,promoting proliferation and metastatic potential of cancer cells in vitro and tumorigenesis in vivo.The application of IL-1β inhibitors is also promising for targeted therapy development in some cancer types.However,as a leukocytic pro-inflammatory cytokine,IL-1β may also possess anti-tumorigenic effects and be type-specific in different cancers.This editorial discusses the up-to-date roles of IL-1β in GI cancers,including underlying mechanisms and down-stream signaling pathways.Understanding and clarifying the roles of IL-1β would significantly benefit future therapeutic targeting and help improve therapeutic outcomes in patients suffering from GI cancer.

Non-coding RNA as future target for diagnose and treatment of perineural invasion in cancers

Perineural invasion(PNI),a particularly insidious form of tumor metastasis distinct from hematogenous or lymphatic spread,has the capacity to extend well beyond the primary tumor site,infiltrating distant regions devoid of lymphatic or vascular structures.PNI often heralds a decrease in patient survival rates and is recognized as an indicator of an unfavorable prognosis across a variety of cancers.Despite its clinical significance,the underlying molecular mechanisms of PNI remain elusive,complicating the development of specific and efficacious diagnostic and therapeutic strategies.In the realm of cancer research,non-coding RNAs(ncRNAs)have attracted considerable attention due to their multifaceted roles and cancer-specific expression profiles,positioning them as promising candidates for applications in cancer diagnostics,prognostics,and treatment.Among the various types of ncRNAs,microRNAs(miRNAs),long non-coding RNAs(lncRNAs),and circular RNAs(circRNAs)have emerged as influential players in PNI.Their involvement is increasingly recognized as a contributing factor to tumor progression and therapeutic resistance.Our study synthesizes and explores the diverse functions and mechanisms of ncRNAs in relation to PNI in cancer.This comprehensive review aims to shed light on cutting-edge perspectives that could pave the way for innovative diagnostic and therapeutic approaches to address the challenges posed by PNI in oncology.

Treatment strategy and therapy based on immune response in patients with gastric cancers

In this editorial,we highlight the significance of a retrospective study“Analysis of the impact of immunotherapy efficacy and safety in patients with gastric cancer and liver metastasis”performed by Liu et al.The authors utilized data collected from gastric cancer(GC)patients and assessed immunotherapy effectiveness and survival status.They found significant differences in treatment response.Because immunotherapy seems to be a beneficial strategy for advanced GC patients,strati-fication of the data based on metastasis status may further improve treatment strategies.

Synchronous gastric and colon cancers:Important to consider hereditary syndromes and chronic inflammatory disease associations

In this editorial we comment on the manuscript,describing management and surveillance strategies in synchronous and metachronous,gastric and colon cancers.Synchronous or metachronous primary malignancies at different sites of the gastrointestinal tract pose a unique diagnostic and therapeutic challenge.Multidisciplinary services and strategies are required for the management of multiple site primary malignancies,to provide the best oncological outcomes.Although this study highlights the dual cancers in 76 sporadic cases,the authors excluded 55 patients due to combination of factors which includes;incomplete clinical data,genetic syndrome,gastric stump cancers.In addition,the authors did not elaborate if any patients presented with signet ring cell morphology,E-cadherin mutations or presence of inflammatory bowel disease.Genetic and mutational errors and epithelial field defects from chronic inflammatory diseases of the gastrointestinal tract are important when considering synchronous gastric and colonic cancers.We will briefly discuss these in this editorial.

Burden of gastrointestinal cancers among working-age population over past thirty years in China

BACKGROUND Although gastrointestinal(GI)cancers have been becoming a great public health concern in China,there is currently a lack of comprehensive literature on the overall burden and changing trends of GI cancers in the working-age population.AIM To assess the burden of GI cancers and to examine the overall,age-and genderspecific trends among the working-age population in China from 1990 to 2019.METHODS Data were extracted from the Global Burden of Disease Study 2019.The burden of GI cancers was indicated by incidence,mortality,disability-adjusted life-years(DALYs),age-standardized incidence rate(ASIR),age-standardized mortality rate,and age-standardized DALYs rate.Trends in the burden of GI cancers from 1990 to 2019 were examined using annual percent change and average annual percent change with Joinpoint regression models.RESULTS For overall GI cancers,a declining trend was observed in the ASIR,age-standardized mortality rate,and agestandardized DALYs rate,with reductions of 0.74%,2.23%,and 2.22%,respectively,from 1999 to 2019 in the Chinese working-age population.However,an increasing trend was observed in the ASIR for overall GI cancers from 2016-2019.The number of either incident cases,mortality cases,and DALYs was higher for colon/rectum cancer and liver cancer in younger participants but lower for esophageal,gallbladder,biliary tract,pancreatic,and stomach cancer among older subjects.Moreover,sex disparity in the GI cancers burden was also examined over 30 years.CONCLUSION The total burden of GI cancers remained heavy among the working-age population in China,although declining trends were observed from 1999 to 2019.Disparities in the GI cancers burden existed between sexes,age groups,and cancer types.Population-based precision prevention strategies are needed to tackle GI cancers among working-age individuals,considering the age,sex,and cancer type disparities in China.

Three novel rare TP53 fusion mutations in a patient with multiple primary cancers:a case report

As survival rates improve and detection technologies advance,the occurrence of multiple primary cancers(MPCs)has been increasing.Approximately 16%of cancer survivors develop a subsequent malignancy,with lung cancer often developing after esophageal cancer due to potential“field cancerization”effects.Despite this observation,the genetic heterogeneity underlying MPCs remains understudied.However,the recent emergence of genetic testing has expanded the scope of investigations into MPCs to investigate signatures underlying cancer predisposition.This report reveals 3 unprecedented TP53 fusion mutations in a Chinese patient afflicted by MPCs,namely,AP1M2–TP53(A1;T11)fusion,TP53–ILF3(T10;I13)fusion,and SLC44A2–TP53(S5;T11)fusion.This patient exhibited an extended period of survival after diagnosis of extensive-stage small cell lung cancer,which occurred 6 years after the diagnosis of esophageal squamous cell cancer.This unique reportmay provide supplementary data that enhance our understanding of the genetic landscape ofMPCs.

Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers

Resveratrol(RSV),the primary polyphenol found in grapes,has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines,including IL-1β,IL-6,IL-1ra and TNFα.Considering the close association between chronic inflammation and cancer development,RSV’s immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation,proliferation,neovascularization,and migration.Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress.In addition to immunomodulation,RSV inhibits cancer development by expressing anti-oxidant effects,causing cell cycle arrest,stimulating the function of certain enzymes,and activating cell signaling pathways.The end outcome is one of the various forms of cell death,including apoptosis,pyroptosis,necroptosis,and more,as it has been observed in vitro.RSV has been shown to act against cancer in practically every organ,while its effects on colon cancer have been documented more frequently.It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol.The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV,with a particular emphasis on cancers of the digestive tract,as a challenge for future clinical research that may contribute to the better prognosis of cancer.

Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers

BACKGROUND Gastric cancer(GC)is the fifth most common and the fourth most lethal malignant tumour in the world.Most patients are already in the advanced stage when they are diagnosed,which also leads to poor overall survival.The effect of posto-perative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence.AIM To investigate the safety and efficacy of a programmed cell death 1(PD-1)inhibitor combined with oxaliplatin and S-1(SOX)in the treatment of Borrmann large type III and IV GCs.METHODS A retrospective analysis(IRB-2022-371)was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy(NAT)from January 2020 to December 2021.According to the different neoadjuvant treatment regimens,the patients were divided into the SOX group(61 patients)and the PD-1+SOX(P-SOX)group(28 patients).RESULTS The pathological response(tumor regression grade 0/1)in the P-SOX group was significantly higher than that in the SOX group(42.86%vs 18.03%,P=0.013).The incidence of ypN0 in the P-SOX group was higher than that in the SOX group(39.29%vs 19.67%,P=0.05).The use of PD-1 inhibitors was an independent factor affecting tumor regression grade.Meanwhile,the use of PD-1 did not increase postoperative complications or the adverse effects of NAT.CONCLUSION A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults:30 years’overview and forecasted trends

BACKGROUND Hepatobiliary and pancreatic(HBP)cancers impose a considerable burden on young populations(aged 15 to 49 years),resulting in a substantial number of new cases and fatalities each year.In young populations,the HBP cancers shows extensive variance worldwide and the updated data in China is lacking.AIM To investigate the current status,trends,projections,and underlying risk factors of HBP cancers among young populations in China.METHODS The Global Burden of Disease Study 2019 provided data on the annual incidence,mortality,disability-adjusted life years(DALYs),age-standardized incidence rate(ASIR),mortality rate(ASMR),and DALYs rate(ASDR)of HBP cancers in young Chinese adults between 1990 and 2019.Temporal trends were assessed using estimated annual percentage change and hierarchical clustering.Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions,with future trends until 2035 projected using the Bayesian age-period-cohort model.RESULTS From 1990 to 2019,incident cases,deaths,DALYs,ASIR,ASMR,and ASDR for liver cancer(LC)in young Chinese individuals decreased,classified into'significant decrease'group.Conversely,cases of gallbladder and biliary tract cancer and pancreatic cancer rose,categorized as either'significant increase'or'minor increase'groups.The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees.Healthy lifestyle behaviors,such as tobacco control,weight management,alcohol moderation,and drug avoidance,could lower HBP cancers incidence.Moreover,except for LC in females,which is likely to initially decline slightly and then rise,the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults.CONCLUSION HBP cancers burden among young adults in China is expected to increase until 2035,necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.

Impact of gynecological cancers on women’s mental health

Gynecological cancers and their treatments are associated with both specific and non-specific long-term physiological effects.Cancer patients face transformations in their lifestyle,body image,role,and social interactions and suffer from physical,psychological,and economic problems.The mental health of cancer patients is of great importance and requires special attention,as growing evidence demonstrates its influence not only on quality of life but also on treatment com-pliance.Gynecological cancers have peculiar psychological consequences,which are linked to the specificity of the site of the neoplasia.Clinicians should be aware of the importance of protecting the psychophysical health of these patients and the fact that their physical health and quality of life also depend on the quality of their mental health.It is possible to structure targeted and effective prevention interventions and treatments to reduce psychological distress and improve the quality of life of subjects living with gynecological cancers.